This invention relates generally to dibutyrylguanosine cyclic phosphate compounds which have been stabilized with respect to decomposition. More particularly, the invention relates to stabilization against decomposition of N.sup.2,2'-O-dibutyrylguanosine-3',5'-cyclic phosphate and salts thereof (hereinafter referred to by the abbreviation DCc - GMP).
In recent years, DBc, - GMP together with guanosine-3',5'-cyclic phosphate and salts thereof have attracted attention as being very useful substances in pharmacology, and uses thereof are being developed as pharmaceutical and medical goods and as reagents for use in biochemical research. Among the numerous advantageous features of DBc - GMP, their high solubility in a large variety of solvents beginning with water and their excellent permeability through cell membranes have been cited.
However, DBc - GMP are unstable at room temperature and even when they are preserved at low temperatures, their rates of decomposition increase further particularly under acidic or alkaline conditions. Under alkaline conditions, DBc - GMP undergo hydrolysis into N.sup.2 -monobutyrylguanosine-3',5'-cyclic phosphate and salts thereof (hereinafter referred to by the abbreviation N.sup.2 -MBc-GMP). Under acidic conditions, on the other hand, DBc - GMP undergo hydrolysis into 2'-O-monobutyrylguanosine-3',5'-cyclic phosphate and salts thereof (hereinafter referred to by the abbreviation 2-O-MBc-GMP). The rates of these hydrolyses increase with the degrees of alkalinity and acidity. ##STR1##
Since DBc - GMP have an unstable property of this nature, they not only require extreme care during the production process with respect to conditions such as temperature and pH level but require particular care also in the preservation of the product. For example, even in the case where DBc - GMP are preserved as solid preparations at a low temperature, it has heretofore been difficult to preserve them in a stable state, and it has been necessary to devise special methods of transportation during handling procedures such as transportation. Because of this unstable character of DBc - GMP, their handling has been difficult, which has been a great obstruction to their development in spite of their usefulness.
As a result of our various researches directed toward overcoming these difficulties and obstruction, we have discovered that when the moisture (water) content of a DBc - GMP in solid state is held at or below 3 percent (all percentages herein being by weight), preferably below 2.5 percent, the DBc - GMP exhibits a high stability, and this discovery is a basis of this invention as described more specifically hereinafter.